Localization of the binding site for the human high-affinity Fc receptor on IgG

A major pathway in the clearance of pathogens involves the coating of the pathogen with specific antibodies, and the binding of the antibody Fc region to cell receptors. This can trigger engulfment of the pathogen by phagocytes or lysis by killer cells. By oligonucleotide site-directed mutagenesis we have engineered a single amino acid change in a mouse IgG2b antibody (Glu 235----Leu) which now enables the antibody to bind to the FcRI (high affinity) receptor on human monocytes with a 100-fold improvement in affinity. This indicates that Leu 235 is a major determinant in the binding of antibody to FcRI and that the receptor may interact directly with the region linking the CH2 domain to the hinge. Tailoring the affinity of antibodies for cell receptors could help dissect their role in clearing pathogen.     

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.     

Fc receptor but not complement binding is important in antibody protection against HIV

Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine. Indeed, passively administered neutralizing antibodies have been shown to protect against HIV challenge in some of the best available animal models. For example, antibodies given intravenously can protect macaques against intravenous or mucosal SHIV (an HIV/SIV chimaera) challenge and topically applied antibodies can protect macaques against vaginal SHIV challenge. However, the mechanism(s) by which neutralizing antibodies afford protection against HIV is not understood and, in particular, the role of antibody Fc-mediated effector functions is unclear. Here we report that there is a dramatic decrease in the ability of a broadly neutralizing antibody to protect macaques against SHIV challenge when Fc receptor and complement-binding activities are engineered out of the antibody. No loss of antibody protective activity is associated with the elimination of complement binding alone. Our in vivo results are consistent with in vitro assays indicating that interaction of Fc-receptor-bearing effector cells with antibody-complexed infected cells is important in reducing virus yield from infected cells. Overall, the data suggest the potential importance of activity against both infected cells and free virus for effective protection against HIV.     

Spectroscopic evidence for a lava fountain driven by previously accumulated magmatic gas

Lava fountains are spectacular continuous gas jets, propelling lava fragments to heights of several hundred metres, which occasionally occur during eruptions of low-viscosity magmas. Whether they are generated by the effervescent disruption of fast-rising bubbly melt or by the separate ascent of a bubble foam layer accumulated at depth still remains a matter of debate. No field measurement has yet allowed firm discrimination between these two models. A key insight into the origin of lava fountains may be gained by measuring the chemical composition of the driving gas phase. This composition should differ markedly depending on whether the magma degassing occurs before or during eruption. Here we report the analysis of magmatic gas during a powerful (250-600 m high) lava fountain, measured with Fourier transform infrared spectroscopy on Mount Etna, Sicily. The abundances of volcanic gas species, determined from absorption spectra of lava radiation, reveal a fountain gas having higher CO2/S and S/Cl ratios than other etnean emissions, and which cannot derive from syn-eruptive bulk degassing of Etna basalt. Instead, its composition suggests violent emptying of a gas bubble layer previously accumulated at about 1.5 km depth below the erupting crater.     

Multiple phosphoglucomutase alleles inToxorhynchites splendens (Diptera: Culcidae)

Summary Multiple phosphoglucomutase (E.C. 2.7.5.1) alleles are found in the mosquitoToxorhynchites splendens. The sample studied reveals 3Pgm alleles whose frequencies are in good accord with Hardy-Weinberg expectations. The most frequent allele is that controlling a phenotype with an intermediate electrophoretic mobility. EachPgm allele determines a two-band electrophoretic pattern.This work is supported in part by a University of Malaya research grant to the senior author.